Advanced stage Hodgkin lymphoma (HL) is usually cured. However, there remains an important fraction of patients who fail therapy, and others who develop late, sometimes fatal, complications of therapy. An intensive treatment regimen results in a higher up front cure rate but at the cost of more second malignancies, fertility loss, and other long-term toxicities. There is a less intensive regimen that yields fewer upfront cures, fewer second malignancies, less fertility loss and fewer long-term toxicities. After taking the result of salvage therapies into account, the approaches generate very similar long term overall survival. If it were possible to target only high risk patients to the more intensive therapy, the upfront cure rate associated with the more intensive therapy might be maintained, while the second malignancies and other toxicities might be minimized in those patients not treated intensively. Our focus in this pilot application is to evaluate previously identified blood-based molecular markers as predictors of response and outcome in patients with advanced HL. We seek to extend the evaluation of molecular markers to include early time points that might be most helpful in guiding decisions about therapy. The markers to be studied will include EBV DNA, sCD30, TARC, sCD163 and sBLyS. We also will evaluate an EBV DNA assay refinement that we anticipate will diminish the noise associated with standard measurements in cell-free blood. The proposed studies will be carried out in the context of a large randomized cooperative group study (E2496) comparing ABVD and Stanford V. The study is complete, clinical and pathologic annotation, and long term outcomes are available.